Induction of collateral circulation after myocardial infarction (MI) is impaired in aging. However, the mechanisms of this impairment are unclear. Possible mechanisms include, but are not limited to, decrease in circulating progenitor/stem cells, decrease in progenitor/stem cells migration, homing, and/or incorporation into the injured tissue, as well as decrease in cytokines/chemokines secreted by the injured myocardium. In addition, clinically, the dysfunction in bone marrow derived endothelial progenitor cells was shown to correlate with increased risk of myocardial infarction. Therefore, the objective of this project is to elucidate the mechanisms and to explore possible interventions to restore the diminished age-associated neo-vascularization in the infarcted myocardium. In this application, we speculated that contribution of bone marrow (BM)-derived progenitor/stem cells to the infarcted myocardial neo-vascularization is compromised in aging and its restoration may rescue cardiac function. In this application stimulation of neo-vascularization in the infarcted myocardium is achieved by either cytokine treatment to mobilize bone marrow cells using G-CSF, grafting a 3-D collagen scaffold onto injured myocardium, or combination of both. To test this hypothesis, we will examine the following specific aims: 1 ) To determine if the age-dependent decrease in cardiac function is associated with diminished neo-vascularization within the infarcted myocardium. 2) To elucidate the possible mechanisms of age-mediated diminished neo-vascularization: 2.1 To determine if the number of mobilized bone marrow cells is decreased in aging after MI and to determine which sub-fraction of EPCs contributes to the cardiac neovascularization after infarction. 2.2 To determine if levels of the cytokines/chemokines released by the infarcted myocardium are decreased in aging. 3) To determine if restoration of the diminished neo-vascularization in the aged rats increases local myocardial blood flow and improves cardiac function. The long-term goal of this project is to rescue cardiac function in the aged heart by restoring enhancing neovascularization within the myocardium after infarction. In this application, Brown Norway Fisher 344 cross (BNXF344) rats at different ages (6 weeks as young, 6 month as adult, and 27 month as old) are used as an aging model and croyinjury of the left ventricle free wall is used as a model of myocardial infarction.